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Lookup NU author(s): Professor Alison Yarnall, Dr Shirley ColemanORCiD, Professor David BurnORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
IntroductionEvidence from clinical and pathological studies suggests a role for both alpha-synuclein and amyloid-beta in the pathophysiology of dementia associated with PD. Recent work demonstrated improvement in memory and reduced amyloid-beta burden in transgenic murine Alzheimer's models given subcutaneous apomorphine. The aim of this work was to determine whether antemortem exposure to apomorphine was associated with lower levels of amyloid-beta in brain tissue in a clinicopathological study of PD.MethodsThe case notes of donors with pathologically proven PD who had (n=36) and had not received apomorphine (n=35) during life for motor complications were reviewed to determine presence or absence of cognitive impairment. The four groups were well matched for disease duration, age at death, sex, and apolipoprotein E4 genotype. The severity of amyloid-beta mature/diffuse plaque load, tau pathology, and alpha-synuclein pathology were all established. Cerebral amyloid angiopathy was determined based on a four-tier grading system.ResultsWithin the cognitively normal cases, significantly reduced amyloid-beta deposition was present in those with antemortem apomorphine exposure; this finding was not replicated in those with cognitive impairment plus previous apomorphine use. In the apomorphine cognitively normal group only, a significant negative association was observed between maximum apomorphine dose received and amyloid-beta burden. Early and maximum doses of apomorphine plus apolipoprotein genotype and sex were significant predictors of total plaque load in an explanatory model.ConclusionThis exploratory study suggests that apomorphine may have a modifying effect on amyloid deposition in nondemented PD cases and thus may represent a potential therapy to reduce cognitive impairment in PD. (c) 2015 Movement Disorder Society
Author(s): Yarnall AJ, Lashley T, Ling H, Lees AJ, Coleman SY, O'Sullivan SS, Compta Y, Revesz T, Burn DJ
Publication type: Article
Publication status: Published
Journal: Movement Disorders
Year: 2016
Volume: 31
Issue: 5
Pages: 668-675
Print publication date: 01/05/2016
Online publication date: 06/08/2015
Acceptance date: 13/10/2015
Date deposited: 25/10/2016
ISSN (print): 0885-3185
ISSN (electronic): 1531-8257
Publisher: John Wiley & Sons, Inc.
URL: http://dx.doi.org/10.1002/mds.26422
DOI: 10.1002/mds.26422
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